Novel Pyrazole Acyl(thio)urea Derivatives Containing a Biphenyl Scaffold as Potential Succinate Dehydrogenase Inhibitors: Design, Synthesis, Fungicidal Activity, and SAR.

As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, a series of new pyrazole acyl(thio)urea compounds containing a diphenyl motif were designed and synthesized. Their structures were confirmed by 1 H NMR, HRMS, and single X-ray crystal diffraction analysis. Most of these compounds possessed excellent activity against 10 fungal plant pathogens at 50 μg mL -1 , especially against Rhizoctonia solani, Alternaria solani , Sclerotinia sclerotiorum , Botrytis cinerea , and Cercospora arachidicola . Interestingly, compounds 3-(difluoromethyl)-1-methyl- N -((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1 H -pyrazole-4-carboxamide ( 9b , EC 50 = 0.97 ± 0.18 μg mL -1 ), 1,3-dimethyl- N -((3',4',5'-trifluoro-[1,1'-biphenyl]-2-yl)carbamoyl)-1 H -pyrazole-4-carboxamide ( 9a , EC 50 = 2.63 ± 0.41 μg mL -1 ), and N -((4'-chloro-[1,1'-biphenyl]-2-yl)carbamoyl)-1,3-dimethyl-1 H -pyrazole-4-carboxamide ( 9g , EC 50 = 1.31 ± 0.15 μg mL -1 ) exhibited activities against S. sclerotiorum that were better than the commercial fungicide bixafen (EC 50 = 9.15 ± 0.05 μg mL -1 ) and similar to the positive control fluxapyroxad (EC 50 = 0.71 ± 0.11 μg mL -1 ). These compounds were not significantly phytotoxic to monocotyledonous and dicotyledonous plants. Structure-activity relationships (SAR) are discussed by substituent effects/molecular docking, and density functional theory analysis indicated that these compounds are succinate dehydrogenase inhibitors.